Near-Infrared II Gold Nanocluster Assemblies with Improved Luminescence and Biofate for In Vivo Ratiometric Imaging of H2S

Ultrasmall gold nanoclusters (AuNCs) are emerging as promising luminescent nanoprobes for bioimaging due to their fantastic photoluminescence (PL) and renal-clearable ability. However, it remains a great challenge to design them for in vivo sensitive molecular imaging in desired tissues. Herein, we have developed a strategy to tailor the PL and biofate of near-infrared II (NIR-II)-emitting AuNCs via ligand anchoring for improved bioimaging. By optimizing the ligand types in AuNCs and using Er3+-doped lanthanide (Ln) nanoparticles as models, core–satellite Ln@AuNCs assemblies were rationally constructed, which enabled 2.5-fold PL enhancement of AuNCs at 1100 nm and prolonged blood circulation compared to AuNCs. Significantly, Ln@AuNCs with dual intense NIR-II PL (from AuNCs and Er3+) can effectively accumulate in the liver for ratiometric NIR-II imaging of H2S, facilitated by H2S-mediated selective PL quenching of AuNCs. We have then demonstrated the real-time imaging evaluation of liver delivery efficacy and dynamics of two H2S prodrugs. This shows a paradigm to visualize liver H2S delivery and its prodrug screening in vivo. Note that Ln@AuNCs are body-clearable via the hepatobiliary excretion pathway, thus reducing potential long-term toxicity. Such findings may propel the engineering of AuNC nanoprobes for advancing in vivo bioimaging analysis.